Untargeted rat brain metabolomics after oral administration of a single high dose of cannabidiol

J Pharm Biomed Anal. 2018 Nov 30;161:1-11. doi: 10.1016/j.jpba.2018.08.021. Epub 2018 Aug 11.


Cannabidiol (CBD), for long time considered as a minor cannabinoid of Cannabis sativa, has recently gained much attention due to its antioxidant, anti-inflammatory, analgesic and anticonvulsant properties. A liquid chromatography coupled to mass spectrometry based method was developed for the quantitative determination of CBD and other cannabinoids (Δ9-tetrahydrocannabinol (THC), 11-hydroxy-THC and 11-nor-9-carboxy-THC) in rat brain samples after oral administration of a single high dose (50 mg/kg) of CBD. The main challenge of the present work was to study CBD pharmacokinetics in rat cortex: the identification of its metabolites and pharmacodynamics through the study of variations in endogenous compounds' concentrations following CBD administration. An untargeted metabolomics approach revealed the formation of some CBD metabolites that are not commonly found in other body tissues or fluids. Lastly, the changes in some endogenous compounds' concentrations were correlated with some of the pharmacological properties of this cannabinoid.

Keywords: Cannabidiol; Cannabidiol metabolites; Cannabidiol pharmacokinetics; Liquid chromatography; Mass spectrometry; Metabolomics.

MeSH terms

  • Animals
  • Brain / metabolism*
  • Cannabidiol / administration & dosage*
  • Cannabidiol / analogs & derivatives
  • Cannabidiol / analysis
  • Cannabidiol / pharmacokinetics*
  • Chromatography, High Pressure Liquid / methods*
  • Dronabinol / analogs & derivatives*
  • Dronabinol / analysis*
  • Metabolomics*
  • Rats
  • Tandem Mass Spectrometry / methods*


  • Cannabidiol
  • 11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid
  • Dronabinol